Although recent advances in perinatal care have brought steady improvement in the mortality rates among preterm neonates, the incidence of neurodevelopmental handicaps in this patient population has not changed over the past decade, and preterm infants with parenchymal involvement of intraventricular hemorrhage are believed to be at high risk for such handicap. The specific aim of this grant application is the investigation of the ability of the cyclo-oxygenase inhibitor of prostaglandin synthesis, indomethacin, to prevent the development of germinal matrix and/or intraventricular hemorrhage (GMH/IVH) in very low birth weight neonates without GMH/IVH at the sixth postnatal hour; secondary specific aims of the proposal include: 1) investigation of the ability of indomethacin to prevent extension of GMH/IVH in those very low birth weight infants found to have low grade GMH/IVH at 6 postnatal hours, 2) investigation of the ability of indomethacin to close the patent ductus arteriosus in very low birth weight neonates, 3) investigation of the ability of indomethacin to promote significant improvement of the pulmonary status of very low birth weight neonates who require assisted ventilation for longer than the first 12 postnatal hours, and 4) investigation of the follow-up neurodevelopmental status of all study infants to determine if there are any long-term sequelae or cerebral protective effects of indomethacin. It is hypothesized that the ability of indomethacin to prevent GMH/IVH in preterm neonates is not related to its effects on the patent ductus arteriosus but rather may be related to its ability to improve pulmonary status. This application proposes a multicenter, placebo-controlled randomized trial to determine if low-dose indomethacin (0.1 mg/kg q 24 hours for 3 doses), beginning at 6 postnatal hours will significantly decrease the incidence of neonatal GMH/IVH in infants not known to have experienced this insult. In a separate, but parallel study, the ability of this agent to alter the risk of the extension of hemorrhage in infants known to have experienced low-grade GMH/IVH at the 6th postnatal hour will be assessed. In order to assess the influence of ductal closure and pulmonary status, serial cardiac ultrasounds will be performed and the ventilatory efficiency index of each infant will be serially monitored. The following parameters monitored for adverse effects of indomethacin: urinary output, serum electrolyte values, platelet count, clinical evidence for excessive bleeding. Long term neurodevelopmental follow-up studies will be performed.